title: A transmembrane form of the prion protein in neurodegenerative disease.
abstract: At the endoplasmic reticulum membrane, the prion protein (PrP) can be synthesized in several topological forms. The role of these different forms was explored with transgenic mice expressing PrP mutations that alter the relative ratios of the topological forms. Expression of a particular transmembrane form (termed CtmPrP) produced neurodegenerative changes in mice similar to those of some genetic prion diseases. Brains from these mice contained CtmPrP but not PrPSc, the PrP isoform responsible for transmission of prion diseases. Furthermore, in one heritable prion disease of humans, brain tissue contained CtmPrP but not PrPSc. Thus, aberrant regulation of protein biogenesis and topology at the endoplasmic reticulum can result in neurodegeneration.
authors.affiliation: Department of Physiology, University of California, San Francisco, CA 94143-0444, USA.
authors.forename: R S
authors.initials: RS
authors.lastname: Hegde
authors.forename: J A
authors.initials: JA
authors.lastname: Mastrianni
authors.forename: M R
authors.initials: MR
authors.lastname: Scott
authors.forename: K A
authors.initials: KA
authors.lastname: DeFea
authors.forename: P
authors.initials: P
authors.lastname: Tremblay
authors.forename: M
authors.initials: M
authors.lastname: Torchia
authors.forename: S J
authors.initials: SJ
authors.lastname: DeArmond
authors.forename: S B
authors.initials: SB
authors.lastname: Prusiner
authors.forename: V R
authors.initials: VR
authors.lastname: Lingappa
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D006224:Cricetinae; D010450:Endopeptidases / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000737:chemistry / Q000378:metabolism*; D016098:Gerstmann-Straussler-Scheinker Disease / Q000378:metabolism; D006801:Humans; D007425:Intracellular Membranes / Q000737:chemistry; D008647:Mesocricetus; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009154:Mutation; D019636:Neurodegenerative Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D018621:PrPC Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018620:PrPSc Proteins / Q000737:chemistry / Q000378:metabolism; D017096:Prion Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D011328:Prions / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011487:Protein Conformation
chemical_list: C110396:(ctm)PrP; D018621:PrPC Proteins; D018620:PrPSc Proteins; D011328:Prions; D010450:Endopeptidases